DESCRIPTION (Applicant's abstract): Failed smoking cessation is a major public health concern because cigarette smoking is the single most important cause of cancer mortality 'in the United States. The goal of this proposal is to examine the impact of nicotine dependence and nicotine withdrawal on the risk for failed smoking cessation in a genetically informative design. We will determine the risk for symptoms of nicotine dependence and withdrawal among successful quitters as compared to failed quitters in a cohort of approximately 4,000 twin pairs of the Vietnam Era Twin (VET) Registry. We will use twin data to estimate the genetic and environmental influences to each symptom of nicotine dependence and withdrawal and the degree to which these influences overlap for risk of failed smoking cessation. We will use latent class analysis to develop dependence and withdrawal profiles and test whether different profiles are predictive of the risk for failed smoking cessation. Finally, we will estimate the genetic and environmental influences to nicotine dependence and nicotine withdrawal profiles that overlap the risk for failed smoking cessation. The VET Registry is a valuable resource for this proposed secondary data analysis because it is a large, nationally distributed, community sample in which a high proportion of members have a history of smoking, failed cessation, nicotine dependence and nicotine withdrawal. This unique sample will provide the power to conduct complex latent class and behavior genetic analysis in a large cohort of middle-aged males.